2,3-dichloro-5-(trifluoromethyl)pyridine (DCTF) is an important organic intermediate for the agrochemical industry in particular for use in the synthesis of fluazinam and fluopicolide as well as other pesticidal active pyridine compounds, e.g. as disclosed in the following patent specification nos. WO 2007/060662-A2, U.S. Pat. No. 6,921,828, and GB 2002368-A. The precursor for this molecule is 2,3-dichloro-5-(trichloromethyl)pyridine (PCMP).
Several methods for production of DCTF are described in the literature, including the use of different starting materials such as 6-hydroxynicotinic acid, 3-picoline, or 2-chloro-5-chloromethylpyridine, routes that pass a common intermediate, i.e. PCMP, towards the final DCTF product.
The production of DCTF starting from 3-picoline-N-oxide can be accomplished by a 4 step synthesis route. The first step of the synthesis is disclosed in U.S. Pat. No. 4,897,488 wherein 2-chloro-5-methylpyridine is synthesized, followed by a radical chlorination step e.g. as described in U.S. Pat. No. 4,241,213, followed by formation of PCMP e.g. as disclosed in U.S. Pat. No. 4,331,811, whereas the final step to DCTF is disclosed in European patent publication number EP 110690-A1.
There are several known methods for the preparation of PCMP, e.g. starting from 2-chloro-5-(trichloromethyl)pyridine using chlorine gas optionally in the presence of various metal based catalysts e.g. as described in U.S. Pat. Nos. 4,636,565, 4,331,811, 4,309,548 and European patent application no. EP 246349-A1. 2-chloro-5-(trichloromethyl)pyridine can be prepared according to the procedure disclosed in U.S. Pat. No. 4,324,627 and European patent application no. EP 4414-A1.
Chlorination of cyanopyridines directly on the pyridine ring is disclosed in patent publication nos. WO 9413640-A1 and U.S. Pat. No. 5,484,929.
Methods for the preparation of 3-trichloromethylpyridines starting from nicotinic acid using various chlorinating agents are described in the following patent publications: U.S. Pat. No. 4,634,771 and EP 281965-A1 and its U.S. Pat. No. 4,833,250.
The use of PCl5 as a chlorinating agent used in the preparation of 3-trichloromethylpyridines is known from e.g. U.S. Pat. No. 4,958,025, disclosing the preparation of 3-trichloromethylpyridines starting from nicotinic acid. In US patent publication no. U.S. Pat. No. 4,419,514 PCl5, is used in combination with phenylphosphonic dichloride as chlorinating agent for the preparation of PCMP starting from 5-chloro-6-hydroxynicotinic acid.
The production of DCTF can also be accomplished in multi-ton scale production starting from 2-chloro-5-(chloromethyl)pyridine (CCMP) as disclosed in Chinese patent publication number CN 101092392. CCMP can be produced from cyclopentadiene in a 6 step synthesis route, but this process has a very poor atom economy and therefore gives rise to a large waste problem as disclosed in U.S. Pat. No. 5,229,519. Nevertheless, it is this 6 step synthesis route starting from cyclopentadiene that is chosen over alternatives, because of the low cost of cyclopentadiene. The world is therefore in need of a high yielding manufacturing procedure starting from a commercially bulk material and producing DCTF in only few synthetic steps.
It is the object of the present invention to provide a method of producing the intermediate product 2,3-dichloro-5-(trichloromethyl)pyridine (PCMP) in high yields and/or with less by-products, notably less by-products of the type that cannot easily be converted into PCMP. Furthermore, the method omits the intermediate reaction product CCMP. Thus, the present invention present a method to produce 2,3-dichloro-5-trichloromethylpyridine (PCMP) in one single step from easily accessible materials, e.g. nicotinic acid (also known as Vitamin B3). The method of the invention may also be conducted without generating any problematic waste and using minimum unit operation.
The intermediate PCMP can be converted to DCTF by a single subsequent step. In a certain embodiment, the invention provides a two-step method which is easy to operate and economical to produce DCTF from the commercially available bulk material nicotinic acid.